Chronic Myeloproliferative DisordersPhase 1NCT00054236
Combination Chemotherapy Followed By Umbilical Cord Blood Transplantation in Treating Patients With Hematologic Cancer or Severe Aplastic Anemia
A Phase 1 study testing anti-thymocyte globulin, filgrastim and cyclophosphamide in people with Chronic Myeloproliferative Disorders and Leukemia, run by Case Comprehensive Cancer Center at 1 site in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Umbilical cord blood transplantation may be able to replace cells destroyed by chemotherapy. Read more about this study
- Who is it for?
- Ages Up to 120 years
- Conditions the study is for
- Chronic Myeloproliferative Disorders, Leukemia, Lymphoma
- What is being tested?
- anti-thymocyte globulin, filgrastim and cyclophosphamide
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteUnited States
- Study dates
- May 2002to Mar 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 120 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
DISEASE CHARACTERISTICS:
- One of the following histologically confirmed diagnoses:
- Acquired severe aplastic anemia
- Meets at least 2 of the following criteria:
- Granulocyte count less than 500/mm^3
- Platelet count less than 20,000/mm^3
- Absolute reticulocyte count less than 20,000/mm^3 (after correction for hematocrit)
- Unresponsive to OR recurrent disease after prior treatment with anti-thymocyte globulin and/or cyclosporine
- Acute myeloid leukemia (AML), meeting 1 of the following criteria:
- Failed induction therapy
- In first complete remission (CR) with any of the following high-risk features:
- Stem cell or biphenotype classification (M0)
- Erythroleukemia (M6)
- Acute megakaryocytic leukemia (M7)
- Cytogenetic markers indicative of poor prognosis
- t(15;17) translocation and failed first-line induction therapy OR there is molecular evidence of persistent disease
- t(8;21) and inv(16) translocations and failed first-line induction therapy
- In early relapse*
- In second or subsequent remission
- Recurrent disease after prior autologous stem cell transplantation (SCT) NOTE: *No refractory relapse
- Acute lymphoblastic leukemia, meeting 1 of the following criteria:
- In early relapse*
- In second or subsequent remission
- In first CR with the following high-risk features:
- t(4;11) or t(9;22) translocation
- Hyperleukocytosis (initial WBC greater than 30,000/mm^3)
- Failed to achieve CR by day 28 of standard induction therapy
- Recurrent disease after prior autologous SCT NOTE: *No refractory relapse
- Chronic myelogenous leukemia
- Chronic or accelerated phase that has failed medical management
- Blastic phase allowed after reinduction chemotherapy induces chronic phase
- Myelodysplastic syndromes meeting 1 of the following criteria:
- Refractory to medical management
- Presence of cytogenetic abnormalities predictive of transformation to acute leukemia, including the following:
= 5q- = 7q-
- Monosomy 7 and trisomy 8
- Evidence of evolution to AML (e.g., refractory anemia with excess blasts [RAEB], or RAEB in transformation)
- Chronic lymphocytic leukemia
- Refractory to treatment including fludarabine-based therapy
- Recurrent disease after prior autologous SCT
- Multiple myeloma
- Recurrent disease after prior autologous SCT
- Beyond first CR or failed induction therapy
- Disease is sensitive to pretransplantation cytoreduction
- Hodgkin's lymphoma
- Beyond first CR or failed induction therapy
- Disease is sensitive to pretransplantation cytoreduction
- Non-Hodgkin's lymphoma (NHL)
- Recurrent disease after prior autologous SCT
- Beyond first CR or failed induction therapy
- Disease is sensitive to pretransplantation cytoreduction
- Mantle zone NHL allowed after induction therapy
- Myeloproliferative disorders
- Refractory to medical management
- Allografting required unless grade 3 or greater myelofibrosis by bone marrow biopsy
- No HLA-matched sibling donor available
- Ineligible for a myeloablative conditioning regimen due to advanced age (over 55), extensive prior therapy, and/or other comorbidities
- If under age 55, must meet at least 1 of the following criteria:
- Received extensive prior therapy
- Organ toxicity or infection precluding eligibility for allogeneic transplantation with full ablation conditioning
- Availability of 2-5 umbilical cord blood units that are at least a 4/6 HLA match
- No active CNS disease
- No primary or grade 3 or 4 myelofibrosis
PATIENT CHARACTERISTICS:
Age
- Any age
Performance status
- Karnofsky 70-100% (for patients 16 years of age and older)
- Lansky 50-100% (for patients under 16 years of age)
Life expectancy
- At least 3 months
Hematopoietic
- See Disease Characteristics
Hepatic
- ALT/AST less than 4 times normal
- Bilirubin less than 2.0 mg/dL (unless due to hepatic infiltration by primary malignancy)
Renal
- Creatinine clearance greater than 40 mL/min
Cardiovascular
- Shortening fraction or ejection fraction greater than 40% of normal value for age by echocardiogram or radionuclide scan
Pulmonary
- FVC and FEV_1 greater than 60% of predicted
- DLCO greater than 60% of predicted (adult patients)
- Clearance by pulmonologist required if patient cannot perform pulmonary function tests
Other
- Not pregnant or nursing
- No uncontrolled active infection (viral, bacterial, or fungal)
- HIV negative
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
- More than 3 months since prior autologous stem cell transplantation
Chemotherapy
- See Disease Characteristics
- At least 4 weeks since prior chemotherapy
Endocrine therapy
- Not specified
Radiotherapy
- Not specified
Surgery
- Not specified
Other
- Recovered from prior therapy
- No other concurrent investigational agents that would preclude study participation or increase risk to patient
- Investigational diagnostic procedures allowed
Trial locations and contacts
1 site in 1 country.
United States1 site
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106-5065
About this study
Official title: Pilot Study Of Multiple Umbilical Cord Blood Unit Transplantation Following Non-Myeloablative Conditioning In Patients With Hematologic Disorders Or Severe Aplastic Anemia
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Umbilical cord blood transplantation may be able to replace cells destroyed by chemotherapy.
PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy followed by umbilical cord blood transplantation in treating patients who have hematologic cancer or severe aplastic anemia.
Read the detailed description
OBJECTIVES:
- Determine the incidence and severity of acute toxicity in patients with hematologic malignancies or severe aplastic anemia treated with a non-myeloablative conditioning regimen followed by umbilical cord blood transplantation.
- Determine the incidence and severity of acute and chronic graft-versus-host-disease in patients treated with this regimen.
- Determine the incidence of relapse, disease-free survival, and overall survival of patients treated with this regimen.
- Determine the survival rate at 100 days post-transplantation in patients treated with this regimen.
- Determine the incidence of regimen-related complications (infection, hepatic veno-occlusive disease, and interstitial pneumonitis) in patients treated with this regimen.
- Determine the incidence of primary and secondary graft failure in patients treated with this regimen.
- Determine the rates and kinetics of donor-derived lymphoid, myeloid, neutrophil, RBC, and platelet engraftment in patients treated with this regimen.
OUTLINE: Patients receive a non-myeloablative conditioning regimen comprising fludarabine IV over 30 minutes on days -8 to -4, cyclophosphamide IV over 2 hours on days -3 to -2, and anti-thymocyte globulin (ATG) IV over at least 4 hours on days -2 to -1. Patients unable to tolerate ATG may receive methylprednisolone IV over 1 hour on days -3 to -1.
Patients undergo multiple unit umbilical cord blood transplantation on days 0-1. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 7 and continuing until blood counts recover.
Patients are followed monthly for 6 months; at 9, 12, 14, 16, 18, and 24 months; and then annually thereafter.
PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study within 2 years.
- Conditions
- Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases
- Being tested
- anti-thymocyte globulin, filgrastim, cyclophosphamide, fludarabine phosphate, umbilical cord blood transplantation
- Keywords
- refractory anemia with excess blasts in transformation, refractory anemia with excess blasts, adult acute myeloid leukemia in remission, childhood acute myeloid leukemia in remission, recurrent adult acute myeloid leukemia, recurrent childhood acute myeloid leukemia, adult erythroleukemia (M6a), childhood acute erythroleukemia (M6), adult acute minimally differentiated myeloid leukemia (M0), childhood acute minimally differentiated myeloid leukemia (M0), adult acute megakaryoblastic leukemia (M7), childhood acute megakaryocytic leukemia (M7), adult acute lymphoblastic leukemia in remission, childhood acute lymphoblastic leukemia in remission, recurrent adult acute lymphoblastic leukemia, recurrent childhood acute lymphoblastic leukemia, accelerated phase chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, previously treated myelodysplastic syndromes, refractory chronic lymphocytic leukemia
- Medical subject headings
- Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma, Neoplasms, Plasma Cell, Myelodysplastic Syndromes, Myelodysplastic-Myeloproliferative Diseases, Anemia, Refractory, with Excess of Blasts
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-thymocyte globulinBiological
anti-thymocyte globulin (ATG) IV over at least 4 hours on days -2 to -1
filgrastimBiological
Patients receive filgrastim (G-CSF) subcutaneously beginning on day 7 and continuing until blood counts recover.
cyclophosphamideDrug
cyclophosphamide IV over 2 hours on days -3 to -2
fludarabine IV over 30 minutes on days -8 to -4
umbilical cord blood transplantationProcedure or surgery
Patients undergo multiple unit umbilical cord blood transplantation on days 0-1.
Patients unable to tolerate ATG may receive methylprednisolone IV over 1 hour on days -3 to -1.
| Study group | Role | What they receive |
|---|---|---|
| non-myeloablative conditioning regimen | Experimental | Not described Receives: Biological: anti-thymocyte globulin; Biological: filgrastim; Drug: cyclophosphamide; Drug: fludarabine phosphate; Procedure: umbilical cord blood transplantation; Drug: methylprednisolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-free survival by disease assessment
Measured: at 28 and 100 days and then at 6, 9, 12, 18, and 24 months
Secondary outcomes (1)
Umbilical cord blood donor engraftment by chimerism and complete blood count (CBC)
Measured: monthly for 6 months and then at 9, 12, 18, and 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2003 (estimated)
- Study startMay 2002
- Primary completionMar 2011
- Study completionMar 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Myeloproliferative DisordersStudies of the same condition, open and under way.
- More trials run by Case Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Brenda Cooper, MD, Principal investigator, Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00054236
- Sponsor's protocol ID
- CWRU6Y01
- Status last verified
- Jul 2020
- First submitted
- 5 Feb 2003
- Last updated
- 27 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study Of Multiple Umbilical Cord Blood Unit Transplantation Following Non-Myeloablative Conditioning In Patients With Hematologic Disorders Or Severe Aplastic Anemia
- ClinicalTrials.gov ID
- NCT00054236
- Acronym / sponsor ID
- CWRU6Y01
- Conditions
- Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases
- Keywords
- refractory anemia with excess blasts in transformation, refractory anemia with excess blasts, adult acute myeloid leukemia in remission, childhood acute myeloid leukemia in remission, recurrent adult acute myeloid leukemia, recurrent childhood acute myeloid leukemia, adult erythroleukemia (M6a), childhood acute erythroleukemia (M6)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- May 2002
- Primary completion
- Mar 2011 (actual)
- Study completion
- Mar 2011 (actual)
- First posted
- 6 Feb 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Umbilical cord blood transplantation may be able to replace cells destroyed by chemotherapy.
PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy followed by umbilical cord blood transplantation in treating patients who have hematologic cancer or severe aplastic anemia.
Detailed description
OBJECTIVES:
- Determine the incidence and severity of acute toxicity in patients with hematologic malignancies or severe aplastic anemia treated with a non-myeloablative conditioning regimen followed by umbilical cord blood transplantation.
- Determine the incidence and severity of acute and chronic graft-versus-host-disease in patients treated with this regimen.
- Determine the incidence of relapse, disease-free survival, and overall survival of patients treated with this regimen.
- Determine the survival rate at 100 days post-transplantation in patients treated with this regimen.
- Determine the incidence of regimen-related complications (infection, hepatic veno-occlusive disease, and interstitial pneumonitis) in patients treated with this regimen.
- Determine the incidence of primary and secondary graft failure in patients treated with this regimen.
- Determine the rates and kinetics of donor-derived lymphoid, myeloid, neutrophil, RBC, and platelet engraftment in patients treated with this regimen.
OUTLINE: Patients receive a non-myeloablative conditioning regimen comprising fludarabine IV over 30 minutes on days -8 to -4, cyclophosphamide IV over 2 hours on days -3 to -2, and anti-thymocyte globulin (ATG) IV over at least 4 hours on days -2 to -1. Patients unable to tolerate ATG may receive methylprednisolone IV over 1 hour on days -3 to -1.
Patients undergo multiple unit umbilical cord blood transplantation on days 0-1. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 7 and continuing until blood counts recover.
Patients are followed monthly for 6 months; at 9, 12, 14, 16, 18, and 24 months; and then annually thereafter.
PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study within 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| non-myeloablative conditioning regimen | Experimental | Biological: anti-thymocyte globulin, Biological: filgrastim, Drug: cyclophosphamide, Drug: fludarabine phosphate, Procedure: umbilical cord blood transplantation, Drug: methylprednisolone |
Who may qualify
- Ages
- Up to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| anti-thymocyte globulinanti-thymocyte globulin (ATG) IV over at least 4 hours on days -2 to -1 | Biological | non-myeloablative conditioning regimen |
| filgrastimPatients receive filgrastim (G-CSF) subcutaneously beginning on day 7 and continuing until blood counts recover. | Biological | non-myeloablative conditioning regimen |
| cyclophosphamidecyclophosphamide IV over 2 hours on days -3 to -2 | Drug | non-myeloablative conditioning regimen |
| fludarabine phosphatefludarabine IV over 30 minutes on days -8 to -4 | Drug | non-myeloablative conditioning regimen |
| umbilical cord blood transplantationPatients undergo multiple unit umbilical cord blood transplantation on days 0-1. | Procedure or surgery | non-myeloablative conditioning regimen |
| methylprednisolonePatients unable to tolerate ATG may receive methylprednisolone IV over 1 hour on days -3 to -1. | Drug | non-myeloablative conditioning regimen |
Primary outcome
Event-free survival by disease assessment
Time frame: at 28 and 100 days and then at 6, 9, 12, 18, and 24 months
1 secondary outcome
Umbilical cord blood donor engraftment by chimerism and complete blood count (CBC)
Time frame: monthly for 6 months and then at 9, 12, 18, and 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brenda Cooper, MD principal investigator
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing anti-thymocyte globulin, filgrastim and cyclophosphamide in people with Chronic Myeloproliferative Disorders and Leukemia, run by Case Comprehensive Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event-free survival by disease assessment (time frame: at 28 and 100 days and then at 6, 9, 12, 18, and 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2020.